Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia☆

Abstract 

Background and purpose

To assess the efficacy and safety of ramelteon, a selective MT₁/MT₂ receptor agonist, for chronic insomnia treatment.

Patients and methods

Randomized, double-blind, placebo-controlled 35-night outpatient trial with weekly clinic visits at multiple centers. Patients include older adults (≥65 years; N=829) with chronic insomnia. Placebo, ramelteon 4mg, or ramelteon 8mg were taken nightly for five weeks, and patient-reported sleep data were collected using sleep diaries. Primary efficacy was sleep latency at week 1. Sustained efficacy was examined at weeks 3 and 5. Rebound insomnia and withdrawal effects were evaluated during a 7-day placebo run-out.

Results

Both doses of ramelteon produced statistically significant reductions in sleep latency vs. placebo at week 1 (ramelteon 4mg: 70.2 vs. 78.5min, P=.008; ramelteon 8mg: 70.2 vs. 78.5min, P=.008). Patients continued to report reduced sleep latency at week 3 with ramelteon 8mg (60.3 vs. 69.3min, P=.003), and at week 5 with ramelteon 4mg (63.4 vs. 70.6min, P=.028) and ramelteon 8mg (57.7 vs. 70.6min; P<.001). Statistically significant increases in total sleep time were observed with ramelteon 4mg at week 1 (324.6 vs. 313.9min, P=.004) and week 3 (336.0 vs. 324.3min, P=.007) compared with placebo. There was no evidence of significant rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was similar among all treatment groups; most were mild or moderate.

Conclusions

In older adults with chronic insomnia, ramelteon significantly reduced patient reports of sleep latency over five weeks of treatment with no significant rebound insomnia or withdrawal effects.

Keywords: Chronic insomnia, Elderly, Ramelteon, Melatonin, Sleep latency, Psychiatric disorders